Abstract
BackgroundThe clinical behaviour of colon cancer is heterogeneous. Five-year overall survival is 50-65% with all stages included. Recurring somatic chromosomal alterations have been identified and some have shown potential as markers for dissemination of the tumour, which is responsible for most colon cancer deaths. We investigated 115 selected stage II-IV primary colon cancers for associations between chromosomal alterations and tumour dissemination.MethodsFollow-up was at least 5 years for stage II-III patients without distant recurrence. Affymetrix SNP 6.0 microarrays and allele-specific copy number analysis were used to identify chromosomal alterations. Fisher’s exact test was used to associate alterations with tumour dissemination, detected at diagnosis (stage IV) or later as recurrent disease (stage II-III).ResultsLoss of 1p36.11-21 was associated with tumour dissemination in microsatellite stable tumours of stage II-IV (odds ratio = 5.5). It was enriched to a similar extent in tumours with distant recurrence within stage II and stage III subgroups, and may therefore be used as a prognostic marker at diagnosis. Loss of 1p36.11-21 relative to average copy number of the genome showed similar prognostic value compared to absolute loss of copies. Therefore, the use of relative loss as a prognostic marker would benefit more patients by applying also to hyperploid cancer genomes. The association with tumour dissemination was supported by independent data from the The Cancer Genome Atlas.ConclusionDeletions on 1p36 may be used to guide adjuvant treatment decisions in microsatellite stable colon cancer of stages II and III.Electronic supplementary materialThe online version of this article (doi:10.1186/1471-2407-14-872) contains supplementary material, which is available to authorized users.
Highlights
The clinical behaviour of colon cancer is heterogeneous
This study aimed to identify Copy Number Alteration (CNA) in colon cancer that may be used at diagnosis to predict risk for tumour dissemination in stage II-III patients
Tumour dissemination was defined as either stage IV with distant metastasis at diagnosis, or stage II-III and recurrence with distant metastasis within 5-years of diagnosis
Summary
The clinical behaviour of colon cancer is heterogeneous. Five-year overall survival is 50-65% with all stages included. Recurring somatic chromosomal alterations have been identified and some have shown potential as markers for dissemination of the tumour, which is responsible for most colon cancer deaths. We investigated 115 selected stage II-IV primary colon cancers for associations between chromosomal alterations and tumour dissemination. Colon cancer is a heterogeneous disease in terms of clinical behaviour with an overall 5-year survival of 50-65%. Colon cancers with microsatellite instability (MSI) have few or no somatic copy number alterations (CNAs). MSS colon cancers frequently have chromosomal instability (CIN) which results in numerous CNAs. Multiple molecular prognostic markers such as MSI (excluding low-level MSI [2,3]), loss of 18q and reduced SMAD4 expression have been suggested [4,5,6,7]. Findings vary considerably between studies and there is no consensus set of CNAs associated with tumour dissemination, i.e. prognosis for patients without metastasis at diagnosis
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